Modified beta-lactamases and methods and uses related thereto

摘要

The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

主权项

1. A method for reducing the likelihood of a beta-lactam antibiotic-induced adverse effect in a subject in need thereof, comprising administering an effective amount of a beta-lactamase to the subject, wherein:
the subject is receiving a beta-lactam antibiotic, the beta-lactam antibiotic being a substrate of the beta-lactamase, the beta-lactamase comprises an amino acid sequence having at 90% sequence identity with SEQ ID NO: 1 and an asparagine (N) or arginine (R) residue at a position corresponding to position 276 according to Ambler classification, and the beta-lactamase hydrolyzes ceftriaxone substantially more efficiently than a beta-lactamase of SEQ ID NO: 1 that has an aspartic acid (D) at a position corresponding to position 276 according to Ambler classification.